Browsing by Subject "methamphetamine"
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Item Changes in the Microbial Community as a Potential Indicator of Clandestine Drug Operations.(2014-05-01) Payne, Tanisha N.; Michael AllenDust is a complex mixture of inorganic and organic materials including diverse microorganisms, which if unattended, accumulates over time. In this study, the microbial content in house dust was tested to determine its forensic detection potential in a model scenario mimicking the conditions of methamphetamine manufacturing. We hypothesized that microorganisms associated with the materials exposed to vapors will respond in a reproducible way. By identifying the microbial communities and any changes that may have occurred we expected to elucidate a correlation between microorganisms and the test chemicals involved, which was supported by the results presented. These findings may provide evidence in otherwise “cold cases” of methamphetamine manufacturer as well as information on the chemistry employed.Item Neurobehavioral and biochemical consequences of chronic, low-dose methamphetamine exposure in male and female mice(2022-08) Davis, Delaney L.; Sumien, Nathalie; Huang, Ren-Qi; Gatch, Michael B.; Phillips, Nicole R.; Schreihofer, Derek A.; Ma, RongAlthough prescription psychostimulants are effective in reducing attention deficit hyperactivity disorder (ADHD) symptomology, misuse of these drugs can pose serious risks such as potential abuse, dependence, and/or neurotoxicity. Of particular concern is that young adults have the highest prevalence of prescription stimulant misuse, with almost 10% of college students admitting to using amphetamine (e.g. Adderall) or methylphenidate (e.g. Ritalin) products. Despite these drugs being widely used for therapeutic and recreational use, the long-term effects of prescription stimulants have not been systematically evaluated in controlled clinical trials. Therefore, it is critical to conduct this research because young adults may be a vulnerable, at-risk population to the potential adverse consequences of long-term amphetamine use. This dissertation research evaluates the biochemical and behavioral consequences of chronic exposure of the prototypical psychostimulant, methamphetamine (METH), in a rodent model. It is hypothesized that repeated doses of METH, within the therapeutic dosing range used in a clinical setting, will induce neurotoxicity through the interplay of biological mechanisms of oxidative stress, glutamate excitotoxicity, neuroinflammation and epigenetic alterations and increase susceptibility to addiction that will be exacerbated by aging processes. Overall, the body of results showed short-term alterations in brain biochemistry and behavioral function, that do not necessarily persist past 5 months after METH treatment. In conclusion, this dissertation highlights the importance of long-term studies in addressing prescription stimulant misuse in an adult population to better understand the safety of these widely used and prescribed psychostimulants.Item The Interaction of Psychostimulant Intake With Brain Aging: Effects On Behavioral Capacity, Oxidative Damage and Dopaminergic Markers(2009-05-01) Hilburn, Craig R.; Forster, Michael J.Frequent abuse of psychostimulants is known to induce changes in brain neurochemistry that are most profound in dopaminergic neurons. These changes could both impair dopamine neurotransmission and adversely affect psychomotor and cognitive functions. One hypothesized cause of these impairments is the adverse effects of psychostimulant-induced increases in oxidative stress. The current studies addressed the general hypothesis that chronic administration of cocaine and methamphetamine would create a change in neurochemistry in dopaminergic neurons and, as a consequence, increase oxidative damage. This would result in decreases in dopaminergic functions specifically in the nigrostriatal region and cause impairments in psychomotor functions. To test this hypothesis we utilized an in vivo rodent model involving continuous chronic administration of cocaine or methamphetamine. Separate groups of mice were exposed to a 30-day treatment, involving continuous infusion of saline, 40 mg/kg of cocaine, or 2 mg/kg of methamphetamine. After discontinuation of the drug treatment, separate groups of the mice were tested for cognitive and psychomotor function at 11, 14, or 16 months of age i.e., 1 week, 3 months, or 5 months after treatment. The test used in this study included spatial learning and memory (swim maze), coordinated running ability (accelerating rotorod), muscle and grip strength (wire suspension) and balance and coordination (bridge walking). Following completion of the behavioral tests brain regions were dissected. The regions we analyzed were the cortex, striatum, cerebellum, hippocampus, midbrain, and hindbrain. These regions were analyzed for carbonyl and thiobarbituric acid reactive substances concentrations to measure levels of protein and lipid oxidation, and Western blotting procedures to address dopaminergic protein expression. Overall, both chronic administration of cocaine and methamphetamine resulted in significant impairments to psychomotor functions. These impairments were evident for both groups on wire hanging tests, bridge walking, and rotating rod tests, both initially following the treatment phase and throughout the age ranges that were analyzed. In addition, the cocaine treatment administered led to profound impairments on cognitive function in the 14-month-old age groups. This impairment was most evident on the reversal phase of the spatial swim maze tests. The biochemical tests revealed that chronic cocaine and methamphetamine administration induced significant increases in protein oxidative damage in the striatum initially following the treatment phase. Psychostimulant-induced lipid oxidative damage was evident in the striatum in both the 14 and 16 month old age groups. Age related declines were evident in the midbrain, cortex and striatum. Overall neither treatment had any effect on the expression of the dopaminergic proteins that were analyzed. The results from these studies warrant the conclusion that chronic cocaine and methamphetamine administration causes an increase in intracellular oxidative damage in the nigrostriatal neurons which decrease dopamine-mediated psychomotor functions. Overall there was not enough evidence to conclude that chronic abuse of these drugs induce impairments that would increase during senescence.Item Trace amine associated receptor 1 (TAAR1), a novel astrocyte receptor for METH-mediated neurotoxicity in HIV-1-associated neurocognitive disorders (HAND)(2015-05-01) Cisneros, Irma E.; Ghorpade, Anuja; Wordinger, Robert J.; Forster, Michael J.This dissertation explores the role of astrocyte trace amine associated receptor 1 (TAAR1), a novel G-protein coupled receptor (GPCR), in modulating the effects of methamphetamine (METH) on astrocyte-mediated excitotoxicity, thereby exacerbating HIV-associated neurocognitive disorders (HAND). The rising pandemic of methamphetamine (METH) abuse has multiple effects and interactions with HIV-1 in infected individuals, affecting both the periphery and the central nervous system (CNS). Moreover, there is a high prevalence of HIV-1 infection among METH users. Underlying evidence provides insight into the cellular mechanisms associated with METH and HIV-1 neurodegeneration, including the effects and byproducts of glial cells, specifically astrocytes. While indirect effects of METH and HIV-1 have been proposed in astrocytes the direct mechanisms by which they contribute to neurodegeneration and continue to evolve. Particularly, imbalance in glutamate homeostasis plays a vital role in METH- & HIV-1-mediated neurodegeneration. We propose METH activates a novel GPCR, trace amine associated receptor 1 (TAAR1), thereby regulating astrocyte-mediated glutamate uptake via excitatory amino acid transporter-2 (EAAT-2), exacerbating HIV-1-induced excitotoxicity. Importantly, our data demonstrate astrocyte functions leading to neurotoxic outcomes like excitotoxicity can be directly exacerbated through TAAR1 regulation. Additionally, extrinsic regulation of TAAR1 signaling, including cAMP, calcium, PKA and PKC, not only reduce activation of subsequent signaling factors, but also reduce or eliminate METH- and IL-1β-mediated alterations in astrocytes glutamate clearance abilities. Finally, preliminary studies indicate that astrocyte-TAAR1 may be a novel therapeutic target for the common morbidity of METH abuse in HAND